This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mitochondria are not only important for the energetic status of the cell, but also the fatal organelles deciding about the cellular life and death. Mitochondria regulate cell death via the expression of pro-apoptotic factors, release of cytochrome c from the mitochondrial inter-membrane space. Oxidative stress, caused in part by mitochondria during the process of oxidative phosphorylation, plays an important role in regulating the function of mitochondria.Oxidative stress has been implicated to several human diseases, including cancer, neurodegenerative disorder, and cardiovascular diseases. Ischemic heart disease, for example, has been linked to oxidative damages to mitochondria of heart cells. It is therefore critical to understand how oxidative stress affects the function of mitochondria. In this project, we propose to study the effects of oxidative stress on mitochondria function relation to apoptosis, using budding yeast as a model organism. The study will focus on Mcd1, a subunit of the cohesin complex. We recently reported (Yang et al., 2008) that upon oxidative stress, Mcd1 is cleaved by a caspase-like protease Eps1. The cleaved C-terminal fragment of Mcd1 is then translocated from nucleus to mitochondria, causing the release of cytochrome c and enhancing the apoptotic cell death. In this proposal, we plan to use cellular, molecular and biochemical techniques to decipher the molecular mechanism of this translocation and its effects on the function of mitochondria.